Chemistry:Emapalumab

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Short description: Monoclonal antibody
Emapalumab
Monoclonal antibody
TypeWhole antibody
SourceHuman
TargetIFN-gamma
Clinical data
Pronunciation/ˈɛməpəlˌuməb/ EM-a-PAL-eu-mab[1]
Trade namesGamifant
Other namesNI-0501, emapalumab-lzsg
AHFS/Drugs.comMonograph
MedlinePlusa619024
License data
Routes of
administration		Intravenous
ATC code
Legal status
Legal status
Identifiers
CAS Number
DrugBank
ChemSpider
  • none
UNII
KEGG
Chemical and physical data
FormulaC6430H9898N1718O2038S46
Molar mass145352.66 g·mol−1

Emapalumab, sold under the brand name Gamifant, is an anti-interferon-gamma (IFNγ) antibody medication used for the treatment of hemophagocytic lymphohistiocytosis (HLH),[3][4][5] which has no cure.[6]

The most common side effects include infections, hypertension, infusion-related reactions, and pyrexia.[3]

The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication.[7]

Medical uses

Emapalumab is used to treat primary hemophagocytic lymphohistiocytosis (HLH) with refractory, recurrent or progressive disease or intolerance with conventional HLH therapy.[3]

Adverse effects

In the clinical trials that lead to emapalumab's FDA approval, the most commonly reported adverse effects were infections (56%), high blood pressure (41%), infusion reactions (27%), and fever (24%).[2][8] Serious adverse effects occurred in about half of the subjects studied in the clinical trial that led to its FDA approval.[8]

Pharmacology

Mechanism of action

In the setting of HLH, over-secretion of IFN-γ is thought to contribute to the pathogenesis of the disease.[2] Emapalumab binds and neutralizes IFN-γ, preventing it from inducing pathological effects.[2]

Pharmacokinetics

Like other antibody-based medications, which are made of amino acid chains called polypeptides, emapalumab is broken down into smaller peptides via the body's normal catabolism.[2]

Society and culture

Legal status

The U.S. Food and Drug Administration (FDA) granted orphan drug designations in 2010 and 2020,[9][10] and breakthrough therapy designation in 2016, on the basis of preliminary data from the phase II trial.[11]

In July 2020, and again in November 2020, the European Medicines Agency (EMA) recommended the refusal of the marketing authorization for emapalumab.[12][13]

Research

The research name of emapalumab was NI-0501.[1] A phase II/III trial began in 2013 and is ongoing (As of August 2018).[14] The trial targets patients under the age of 18 who have failed to improve on conventional treatments.[15] This study was realised in the context of an EU-funded FP7 project, named FIGHT-HLH (306124).[citation needed]

References

  1. ↑ 1.0 1.1 "STATEMENT ON A NONPROPRIETARY NAME ADOPTED BY THE USAN COUNCIL". https://searchusan.ama-assn.org/usan/documentDownload?uri=%2Funstructured%2Fbinary%2Fusan%2Femapalumab.pdf. 
  2. ↑ 2.0 2.1 2.2 2.3 2.4 "Gamifant (- emapalumab-lzsg injection". 30 June 2020. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a865e0ef-8685-4f69-8838-648c4f3bab47. 
  3. ↑ 3.0 3.1 3.2 "FDA approves emapalumab for hemophagocytic lymphohistiocytosis". 20 November 2018. https://www.fda.gov/drugs/fda-approves-emapalumab-hemophagocytic-lymphohistiocytosis.  This article incorporates text from this source, which is in the public domain.
  4. ↑ "FDA Approves Gamifant (emapalumab-lzsg), the First and Only Treatment Indicated for Primary Hemophagocytic Lymphohistiocytosis (HLH)" (Press release). Sobi. 20 November 2018. Retrieved 21 November 2018 – via Business Wire.
  5. ↑ "Emapalumab for the treatment of hemophagocytic lymphohistiocytosis". Drugs of Today 56 (7): 439–446. July 2020. doi:10.1358/dot.2020.56.7.3145359. PMID 32648854. 
  6. ↑ Clinical trial number NCT02069899 for "Long-term Follow-up of HLH Patients Who Received Treatment With NI-0501, an Anti-interferon Gamma Monoclonal Antibody" at ClinicalTrials.gov
  7. ↑ (PDF) New Drug Therapy Approvals 2018 (Report). January 2019. https://www.fda.gov/media/120357/download. Retrieved 16 September 2020. 
  8. ↑ 8.0 8.1 "Emapalumab Approved for Rare Primary Hemophagocytic Lymphohistiocytosis". https://www.raredr.com/news/emapalumab-approved-for-rare-primary-hemophagocytic-lymphohistiocytosis. 
  9. ↑ "Emapalumab Orphan Drug Designations and Approvals". 25 September 2020. https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=766720. 
  10. ↑ "Emapalumab Orphan Drug Designations and Approvals". 26 March 2010. https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=302910. 
  11. ↑ "Novimmune's NI-0501 Granted Breakthrough Therapy Designation by US FDA for Treatment of Patients With Primary Hemophagocytic Lymphohistiocytosis (HLH) - FierceBiotech". 16 March 2016. http://www.fiercebiotech.com/biotech/novimmune-s-ni-0501-granted-breakthrough-therapy-designation-by-us-fda-for-treatment-of. 
  12. ↑ "Gamifant: Pending EC decision". 24 July 2020. https://www.ema.europa.eu/en/medicines/human/summaries-opinion/gamifant. 
  13. ↑ "Gamifant EPAR". 21 July 2020. https://www.ema.europa.eu/en/medicines/human/EPAR/gamifant. 
  14. ↑ Clinical trial number NCT01818492 for "A Study to Investigate the Safety and Efficacy of an Anti-IFNγ mAb in Children Affected by Primary Haemophagocytic Lymphohistiocytosis" at ClinicalTrials.gov
  15. ↑ "NI-0501: A Study to Investigate the Safety and Efficacy of an Anti-IFN? mAb in Children Affected by Primary Hemophagocytic Lymphohistiocytosis". https://www.cincinnatichildrens.org/service/c/clinical-trials/studies/ni-0501-study. 

External links

  • Clinical trial number NCT01818492 for "A Study to Investigate the Safety and Efficacy of an Anti-IFNγ mAb in Children Affected by Primary Haemophagocytic Lymphohistiocytosis" at ClinicalTrials.gov



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